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0 °C

The (S)-N-[[3-[3-fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (263 mg, 0.67 mmol) was slurried in dry CH2Cl2 (10 mL) and cooled to 0° C. in an ice bath. The soluton became homogeneous after the addition of the pyridine (0.216 mL, 2.67 mmol). Next, the methoxyacetyl chloride (0.064 mL, 0.69 mmol) was added drop wise. The reaction was stirred at 0° C. for 30 minutes and then the ice bath was removed. After one hour, the reaction was found to be complete by TLC (10% MeOH/CHCl3, UV short wave). The reaction mixture was diluted with CH2Cl2 (100 mL) and then washed with 1N HCl/brine (50 mL each), saturated NaHCO3 /brine (50 mL each), and brine (100 mL). Each aqueous portion was back-extracted with more CH2Cl2 (2×25 mL). The organic layers were combined, dried over anhydrous NaSO4, filtered, and concentrated under reduced pressure to give an orange solid. This solid was chromatographed on silica gel (35 g,) eluting with a gradient of 1-5% MeOH in 10% CH3CN/CHCl3 to give an orange solid. The latter solid was recrystallized by dissolving it in a minimal amount of CH2Cl2 /MeOH and then triturating with ether to yield 158 mg (51%) of the title compound as an off-white solid with a melting point of 147°-148° C. Aqueous solubility (pH 7, phosphate buffer) was 6.4 mg/ml.

1. customthe ice bath was removed
2. waitAfter one hour
3. additionThe reaction mixture was diluted with CH2Cl2 (100 mL)
4. washwashed with 1N HCl/brine (50 mL each), saturated NaHCO3 /brine (50 mL each), and brine (100 mL)
5. extractionEach aqueous portion was back-extracted with more CH2Cl2 (2×25 mL)
6. dry with materialdried over anhydrous NaSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give an orange solid
10. customThis solid was chromatographed on silica gel (35 g,)
11. washeluting with a gradient of 1-5% MeOH in 10% CH3CN/CHCl3
12. customto give an orange solid
13. customThe latter solid was recrystallized
14. dissolutionby dissolving it in a minimal amount of CH2Cl2 /MeOH
15. customtriturating with ether